A novel role of the CX3 CR1/CX3 CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment

E. Ferretti, M. Bertolotto, S. Deaglio, C. Tripodo, D. Ribatti, V. Audrito, F. Blengio, S. Matis, S. Zupo, D. Rossi, L. Ottonello, G. Gaidano, F. Malavasi, V. Pistoia, A. Corcione

Research output: Contribution to journalArticlepeer-review


Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX3 CR1/CX3 CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX3 CR1 and CX3 CL1 and released constitutively soluble CX3 CL1. One third of these were attracted in vitro by soluble CX3 CL1. CX3 CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX 3 CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX3 CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX 3 CL1 was expressed by CLL cells whereas CX3 CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX3 CR1 and CX3 CL1, but did not secrete soluble CX3 CL1. Only half of NLC cell fractions were attracted in vitro by CX3 CL1. In conclusion, the CX3 CR1/CX3 CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.

Original languageEnglish
Pages (from-to)1268-1277
Number of pages10
Issue number8
Publication statusPublished - Aug 2011


  • chemokines
  • chronic lymphocytic leukemia (CLL)
  • nurselike cells (NLCs)
  • tumor microenvironment

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine
  • Medicine(all)

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